Adenosine A1 receptor antisense infused in striatum of rats: actions on alcohol-induced locomotor impairment, blood alcohol, and body temperature

Abstract

Previous pharmacological studies show that adenosine receptors in the corpus striatum may be involved in locomotor coordination. The purpose of this investigation was to determine whether the adenosine A1 receptor subtype would alter the locomotor response due to incapacitating doses of alcohol. In these experiments, an antisense oligodeoxynucleotide (ODN) targeted to the adenosine A1 receptor was used to elucidate its possible role in locomotor function. After bilateral cannulation of the caudate nuclei of two strains of adult male rats, the animals were trained to remain on a rotorod for an entire 3-min interval. Then, a standard dose of 2.0 micrograms per 2.0 microliters of the A1 adenosine antisense (A1AS), dissolved in a pyrogen-free artificial cerebrospinal fluid (aCSF), was microinjected four times bilaterally into the caudate nuclei of the rats at successive 12-h intervals over 2 days. Three sets of controls were utilized: intragastric gavage with tap water alone: intragastric gavage of 3.5-4.0 g/kg 20% alcohol alone; and the aCSF vehicle alone microinjected identically in the caudate nuclei. The results showed that the intragastric administration of 20% alcohol in a dose of 3.5-4.0 g/kg caused a complete incapacitation of locomotor performance. Moreover, the A1AS injected in the striatum failed to alter significantly the action of alcohol in its impairment of the rats' ability to negotiate the rotorod. Concurrent measures of blood alcohol and body temperature taken to validate the efficacy of alcohol administration correlated precisely with the blockade of locomotor behavior of the animals. These findings thus suggest that because of the specificity of the A1AS probe, the A1 receptor in the striatum is not involved in the alcohol-induced incapacitation of locomotor activity.